| Project/Area Number |
18K17225
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 57060:Surgical dentistry-related
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| Research Institution | Okayama University |
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Principal Investigator |
Okui Tatsuo 岡山大学, 大学病院, 助教 (40610928)
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| Project Period (FY) |
2018-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2019: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2018: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
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| Keywords | HMGB1 / がん性疼痛 / 破骨細胞 / 知覚神経 / 癌骨破壊 / 骨痛 |
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| Outline of Final Research Achievements |
Oral cancer (OCa) invades to bone and causes bone pain. bone pain thus poses a significant challenge to the quality of life of patients presenting with OCa-BP. Here we studied OCa bone pain (OCa-BP) in an intratibial mouse xenograft model that uses a BCa cell line (SAS cells). These mice develop OCa-BP associated with an upregulation of phosphorylated ERK1/2 (pERK1/2), which is a molecular indicator of neuron excitation in the dorsal root ganglia (DRGs) of sensory nerve cell bodies. Our experiments demonstrated that inhibition of High mobility group box1(HMGB1) by short hairpin (shRNA) transduction, HMGB1 neutralizing antibody and HMGB1 receptor antagonist suppressed the OCa-BP and the pERK1/2 expression in DRG. Collectively, our results show that HMGB1 originating Bca evokes BCa-BP via direct HMGB1 signaling and hypersensitization for acid environment in SNs.
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| Academic Significance and Societal Importance of the Research Achievements |
臨床的にがんの大きさとがん性疼痛強度は相関しない場合が多く、また神経浸潤(PNI)を示すがん患者は予後不良であることから神経とがんの相互作用は予想されていたが、がん性疼痛の分子生物学的な検索は、実験手技の複雑さや電気生理学的な実験手技と分子生物学的な実験手技の差異からピットフォールになっている分野であった。報告者の検討により腫瘍細胞が産生するHMGB1により神経細胞の興奮が惹起され骨痛が増強されることを分子生物学、電気生理学的手法を用いて世界で初めて報告し、研究結果は社会的に重要なインパクトを持つと予想できる。
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